The focus of this project is the measurement and modulation of angiogenic activity in astrocytomas. Angiogenesis, the process by which capillary growth occurs, is necessary for tumor growth and metastasis. Until now, we have had no way to measure angiogenesis or to inhibit angiogenesis because in vitro studies suggest that the growth autonomy of brain tumors may be dependent on expression of angiogenic factors. We have developed and standardized in our laboratory an immunologic assay for basic fibroblast growth factor (bFGF) that has been used to screen serum, urine, CSF, and brain tumor cyst fluid. Standardization of an assay for acidic FGF is on-going. Preliminary results suggest that bFGF is elevated in the serum and urine of cancer patients, as compared to normal controls. Elevated bFGF has also been detected in the CSF of patients with astrocytomas, as compared to patients without CNS malignancies. We plan to screen all newly diagnosed adult and pediatric patients at DFCI, CH, and BWH with astrocytomas for bFGF (and aFGF, when available) and to correlate these results with pattern of failure and survival. We will also follow FGF levels with changes in disease status. Until recently there has been no means to inhibit angiogenic activity as an anti-cancer therapy. A newly developed synthetic antibiotic, AGN-1470, is a potent inhibitor of angiogenesis. In animal studies, AGM-1470 has been well tolerated and effective. We will conduct a Phase I study of this drug in patients with relapsed astrocytomas. Once the maximally tolerated dose has been established, we will implement a Phase II study. Simultaneously, we will evaluate the efficacy of AGM-1470 in combination with various chemotherapeutic agents and radiation in a rat brain tumor model.